Beat-to-beat dynamic regulation of intracellular pH in cardiomyocytes

Yankun Lyu, Phung N. Thai, Lu Ren, Valeriy Timofeyev, Zhong Jian, Seojin Park, Kenneth S Ginsburg, James Overton, Julie Bossuyt, Donald M. Bers, Ebenezer N. Yamoah, Ye Chen-Izu, Nipavan Chiamvimonvat, Xiaodong Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

The mammalian heart beats incessantly with rhythmic mechanical activities generating acids that need to be buffered to maintain a stable intracellular pH (pHi) for normal cardiac function. Even though spatial pHi non-uniformity in cardiomyocytes has been documented, it remains unknown how pHi is regulated to match the dynamic cardiac contractions. Here, we demonstrated beat-to-beat intracellular acidification, termed pHi transients, in synchrony with cardiomyocyte contractions. The pHi transients are regulated by pacing rate, Cl/HCO3- transporters, pHi buffering capacity, and β-adrenergic signaling. Mitochondrial electron-transport chain inhibition attenuates the pHi transients, implicating mitochondrial activity in sculpting the pHi regulation. The pHi transients provide dynamic alterations of H+ transport required for ATP synthesis, and a decrease in pHi may serve as a negative feedback to cardiac contractions. Current findings dovetail with the prevailing three known dynamic systems, namely electrical, Ca2+, and mechanical systems, and may reveal broader features of pHi handling in excitable cells.

Original languageEnglish (US)
Article number103624
JournaliScience
Volume25
Issue number1
DOIs
StatePublished - Jan 21 2022

Keywords

  • Cardiovascular medicine
  • Molecular biology
  • Molecular dynamics

ASJC Scopus subject areas

  • General

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